The etiology and pathogenesis of primary hepatomas remain largely unknown. The extrahepatic administration of diethylnitrosamine to rats results in the development of a high incidence of primary liver tumors. The major objective of this research is to investigate both genetic and epigenetic alterations induced by diethylnitrosamine in the normal cellular regulatory circuits which govern selective gene expression. Several model systems are being used in the proposed research to study diethylnotrosamine induced alterations in differential gene expression. These model systems include the following: Normal rat liver; chemically or surgically induced regenerating rat liver; rat liver undergoing chemically induced neoplastic transformation; fetal rat liver; and fully developed diethylnitrosamine induced rat hepatomas. Nucleic acid hybridization techniques are being employed to quantitatively monitor general changes in the genetic expression of both repetitive and unique RNA transcripts. In addition, nucleic acid reassociation procedures are being used to monitor alterations in the expression of the genes which code for rat serum albumin and alpha-fetoprotein in normal, proliferating, fetal and carcinogen exposed rat liver cells.